FAF1 Gene Involvement in Pituitary Corticotroph Tumors.

Cushing's disease (CD) is caused by rare pituitary corticotroph tumors that lead to corticotropin (ACTH) excess. Variants in FAF1, a pro-apoptotic protein involved in FAS-induced cell death, have been implicated in malignant disorders but the involvement of FAF1 in pituitary tumors has not been studied. Genetic data from patients with CD were reviewed for variants in FAF1 gene. Knockout mice (KO) were followed to assess the development of any pituitary disorder or cortisol excess. AtT-20 cells were used to study the effects of the variants of interest on ACTH secretion and cell proliferation. Three variants of interest were identified in 5 unique patients, two of which had rare allele frequency in genomic databases and were predicted to be likely pathogenic. KO mice were followed over time and no difference in their length/weight was noted. Additionally, KO mice did not develop any pituitary lesions and retained similar corticosterone secretion with wild type. AtT-20 cells transfected with FAF1 variants of interest or WT expression plasmids showed no significant difference in cell death or Pomc gene expression. However, in silico prediction models suggested significant differences in secondary structures of the produced proteins. In conclusion, we identified two FAF1 variants in patients diagnosed with CD with a potential pathogenic effect on the protein function and structure. Our in vitro and in vivo studies did not reveal an association of FAF1 defects with pituitary tumorigenesis and further studies may be needed to understand any association.

Genomic and sequence variants of protein kinase A regulatory subunit type 1ß (PRKAR1B) in patients with adrenocortical disease and Cushing syndrome.

PURPOSE: Protein kinase A (PKA) subunit defects (in PRKAR1A and PRKACA) are known to contribute to adrenal tumor pathogenesis. We studied the PRKAR1B gene for any genetic changes in bilateral adrenocortical hyperplasia (BAH) and cortisol-producing adrenal adenomas (CPA). METHODS: Exome sequencing and PRKAR1B copy-number variant (CNV) analysis were performed in 74 patients with BAH and 21 with CPA. PKA activity was studied in tumors with defects; sequence variants were investigated in vitro. RESULTS: Three PRKAR1B germline variants (p.I40V, p.A67V, p.A300T) were identified among 74 patients with BAH. PRKAR1B copy-number gains (CNG) were found in 3 of 21 CPAs, one in a tumor carrying a somatic PRKACA "hotspot" pathogenic variant p.L206R. CPAs bearing PRKAR1B CNGs showed higher PRKAR1B messenger RNA (mRNA) levels and reduced PKA activity. Baseline PKA activity was also decreased for p.A67V and p.A300T in vitro, and mutant PRKAR1ß bound PRKACα in fluorescence resonance energy transfer (FRET) recordings of cotransfected HEK293 cells stronger than normal. CONCLUSION: PRKAR1B is yet another PKA subunit that may potentially contribute to adrenal tumor formation. Its involvement in adrenocortical disease may be different from that of other subunits, because PRKAR1B variants and PRKAR1B CNGs were associated with decreased (rather than increased) overall PKA activity in vitro.

A phosphodiesterase 11 (Pde11a) knockout mouse expressed functional but reduced Pde11a: Phenotype and impact on adrenocortical function.

Phosphodiesterases catalyze the hydrolysis of cyclic nucleotides and maintain physiologic levels of intracellular concentrations of cyclic adenosine and guanosine mono-phosphate (cAMP and cGMP, respectively). Increased cAMP signaling has been associated with adrenocortical tumors and Cushing syndrome. Genetic defects in phosphodiesterase 11A (PDE11A) may lead to increased cAMP signaling and have been found to predispose to the development of adrenocortical, prostate, and testicular tumors. A previously reported Pde11a knockout (Pde11a-/-) mouse line was studied and found to express PDE11A mRNA and protein still, albeit at reduced levels; functional studies in various tissues showed increased cAMP levels and reduced PDE11A activity. Since patients with PDE11A defects and Cushing syndrome have PDE11A haploinsufficiency, it was particularly pertinent to study this hypomorphic mouse line. Indeed, Pde11a-/- mice failed to suppress corticosterone secretion in response to low dose dexamethasone, and in addition exhibited adrenal subcapsular hyperplasia with predominant fetal-like features in the inner adrenal cortex, mimicking other mouse models of increased cAMP signaling in the adrenal cortex. We conclude that a previously reported Pde11a-/- mouse showed continuing expression and function of PDE11A in most tissues. Nevertheless, Pde11a partial inactivation in mice led to an adrenocortical phenotype that was consistent with what we see in patients with PDE11A haploinsufficiency.

Inhibition of Aurora kinase A activity enhances the antitumor response of beta-catenin blockade in human adrenocortical cancer cells.

Adrenocortical cancer (ACC) is a rare and aggressive type of endocrine tumor with high risk of recurrence and metastasis. The overall survival of patients diagnosed with ACC is low and treatment for metastatic stages remain limited to mitotane, which has low efficiency in advanced stages of the disease and is associated with high toxicity. Therefore, identification of new biological targets to improve ACC treatment is crucial. Blockade of the Wnt/beta-catenin pathway decreased adrenal steroidogenesis and increased apoptosis of NCI-H295 human ACC cells, in vitro and in a xenograft mouse model. Aurora kinases play important roles in cell division during the G1-M phase and their aberrant expression is correlated with a poor prognosis in different types of tumors. Hence, we hypothesized that inhibition of aurora kinases activity combined with the beta-catenin pathway blockade would improve the impairment of ACC cell growth in vitro. We studied the combinatorial effects of AMG 900, an aurora kinase inhibitor and PNU-74654, a beta-catenin pathway blocker, on proliferation, survival and tumor progression in multiple ACC cell lines: NCI-H295, CU-ACC1 and CU-ACC2. Exposure of ACC cells to the combination of AMG 900 with PNU-74654 decreased cell proliferation and viability compared to either treatment alone. In addition, AMG 900 inhibited cell invasion and clonogenesis compared to PNU-74654, and the combination showed no greater effects. In contrast, PNU-74654 was more effective in decreasing cortisol secretion. These data suggest that inhibition of aurora kinases activity combined with blockade of the beta-catenin pathway may provide a combinatorial approach for targeting ACC tumors.

Volumetric Modeling of Adrenal Gland Size in Primary Bilateral Macronodular Adrenocortical Hyperplasia.

CONTEXT: Radiological characterization of adrenal size in primary bilateral macronodular adrenocortical hyperplasia (PBMAH) has not been previously investigated. OBJECTIVE: We hypothesized that volumetric modeling of adrenal gland size may correlate with biochemical disease severity in patients with PBMAH. Secondary analysis of patients with concurrent primary aldosteronism (PA) was performed. DESIGN: A retrospective cross-sectional analysis of 44 patients with PBMAH was conducted from 2000 to 2019. SETTING: Tertiary care clinical research center. PATIENTS: Patients were diagnosed with PBMAH based upon clinical, genetic, radiographic and biochemical characteristics. INTERVENTION: Clinical, biochemical, and genetic data were obtained. Computed tomography scans were used to create volumetric models by manually contouring both adrenal glands in each slice using Vitrea Core Fx v6.3 software (Vital Images, Minnetonka, Minnesota). MAIN OUTCOME AND MEASURES: 17-hydroxycorticosteroids (17-OHS), ARMC5 genetics, and aldosterone-to-renin ratio (ARR) were retrospectively obtained. Pearson test was used for correlation analysis of biochemical data with adrenal volume. RESULTS: A cohort of 44 patients with PBMAH was evaluated, with a mean age (±SD) of 53 ±â€…11.53. Eight patients met the diagnostic criteria for PA, of whom 6 (75%) were Black. In the Black cohort, total adrenal volumes positively correlated with midnight cortisol (R = 0.76, P = 0.028), urinary free cortisol (R = 0.70, P = 0.035), and 17-OHS (R = 0.87, P = 0.0045), with a more pronounced correlation with left adrenal volume alone. 17-OHS concentration positively correlated with total, left, and right adrenal volume in patients harboring pathogenic variants in ARMC5 (R = 0.72, P = 0.018; R = 0.65, P = 0.042; and R = 0.73, P = 0.016, respectively). CONCLUSIONS: Volumetric modeling of adrenal gland size may associate with biochemical severity in patients with PBMAH, with particular utility in Black patients.

ARMC5 variants in PRKAR1A-mutated patients modify cortisol levels and Cushing's syndrome.

Mutations in the protein kinase A (PKA) regulatory subunit type 1A (PRKAR1A) and armadillo repeat-containing 5 (ARMC5) genes cause Cushing's syndrome (CS) due to primary pigmented nodular adrenocortical disease (PPNAD) and primary bilateral macronodular adrenocortical hyperplasia (PBMAH), respectively. Between the two genes, ARMC5 is highly polymorphic with several variants in the population, whereas PRKAR1A has very little, if any, non-pathogenic variation in its coding sequence. We tested the hypothesis that ARMC5 variants may affect the clinical presentation of PPNAD and CS among patients with PRKAR1A mutations. In this study, 91 patients with PPNAD due to PRKAR1A mutations were tested for abnormal cortisol secretion or CS and for ARMC5 sequence variants. Abnormal cortisol secretion was present in 71 of 74 patients with ARMC5 variants, whereas 11 of 17 patients negative for ARMC5 variants did not have hypercortisolemia. The presence of ARMC5 variants was a statistically strong predictor of CS among patients with PRKAR1A mutations (P < 0.001). Among patients with CS due to PPNAD, ARMC5 variants were associated with lower cortisol levels at baseline (P = 0.04) and after high dose dexamethasone administration (P = 0.02). The ARMC5 p.I170V variant increased ARMC5 protein accumulation in vitro and decreased viability of NCI-H295 cells (but not HEK 293T cells). PPNAD tissues with ARMC5 variants showed stronger ARMC5 protein expression than those that carried a normal ARMC5 sequence. Taken together, our results suggest that ARMC5 variants among patients with PPNAD due to PRKAR1A defects may play the role of a genetic modifier for the presence and severity of hypercortisolemia.

ARMC5 Alterations in Patients With Sporadic Neuroendocrine Tumors and Multiple Endocrine Neoplasia Type 1 (MEN1).

CONTEXT: Adrenal lesions are frequent among patients with sporadic neuroendocrine tumors (spNETs) or multiple endocrine neoplasia type 1 (MEN1). Armadillo repeat-containing 5 (ARMC5)-inactivating variants cause adrenal tumors and possibly other neoplasms. OBJECTIVE: The objective of this work is to investigate a large cohort spNETs or MEN1 patients for changes in the ARMC5 gene. PATIENTS AND METHODS: A total of 111 patients, 94 with spNET and 17 with MEN1, were screened for ARMC5 germline alterations. Thirty-six tumors (18 spNETs and 18 MEN1 related) were collected from 20 patients. Blood and tumor DNA samples were genotyped using Sanger sequencing and microsatellite markers for chromosomes. ARMC5 and MEN1 expression were assessed by immunohistochemistry. RESULTS: In 76 of 111 (68.4%) patients, we identified 16 different ARMC5 germline variants, 2 predicted as damaging. There were no differences in the prevalence of ARMC5 variants depending on the presence of MEN1-related adrenal lesions. Loss of heterozygosity (LOH) at chromosome 16p and ARMC5 germline variants were present together in 23 or 34 (67.6%) tumors; in 7 of 23 (30.4%) their presence led to biallelic inactivation of the ARMC5 gene. The latter was more prevalent in MEN1-related tumors than in spNETs (88.9% vs 38.9%; P = .005). LOH at the chromosome 16p (ARMC5) and 11q (MEN1) loci coexisted in 16/18 MEN1-related tumors, which also expressed lower ARMC5 (P = .02) and MEN1 (P = .01) proteins compared to peritumorous tissues. CONCLUSION: Germline ARMC5 variants are common among spNET and MEN1 patients. ARMC5 haploinsufficiency or biallelic inactivation in spNETs and MEN1-related tumors suggests that ARMC5 may have a role in modifying the phenotype of patients with spNETs and/or MEN1 beyond its known role in macronodular adrenocortical hyperplasia.

Mass spectrometry-based steroid profiling in primary bilateral macronodular adrenocortical hyperplasia.

Biochemical characterization of primary bilateral macronodular adrenocortical hyperplasia (PBMAH) by distinct plasma steroid profiles and its putative correlation to disease has not been previously studied. LC-MS/MS-based steroid profiling of 16 plasma steroids was applied to 36 subjects (22 females, 14 males) with PBMAH, 19 subjects (16 females, 3 males) with other forms of adrenal Cushing's syndrome (ACS), and an age and sex-matched control group. Germline ARMC5 sequencing was performed in all PBMAH cases. Compared to controls, PBMAH showed increased plasma 11-deoxycortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycortisol, and aldosterone, but lower progesterone, DHEA, and DHEA-S with distinct differences in subjects with and without pathogenic variants in ARMC5. Steroids that showed isolated differences included cortisol and 18-oxocortisol with higher (P < 0.05) concentrations in ACS than in controls and aldosterone with higher concentrations in PBMAH when compared to controls. Larger differences in PBMAH than with ACS were most clear for corticosterone, but there were also trends in this direction for 18-hydroxycortisol and aldosterone. Logistic regression analysis indicated four steroids - DHEA, 11-deoxycortisol, 18-oxocortisol, and corticosterone - with the most power for distinguishing the groups. Discriminant analyses with step-wise variable selection indicated correct classification of 95.2% of all subjects of the four groups using a panel of nine steroids; correct classification of subjects with and without germline variants in ARMC5 was achieved in 91.7% of subjects with PBMAH. Subjects with PBMAH show distinctive plasma steroid profiles that may offer a supplementary single-test alternative for screening purposes.

High expression of adrenal P450 aromatase (CYP19A1) in association with ARMC5-primary bilateral macronodular adrenocortical hyperplasia.

Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a rare cause of ACTH-independent Cushing syndrome (CS), which has been associated with ectopic G-protein coupled receptors (GPCRs) in the adrenal cortex. We recently studied a 51-year-old male with PBMAH who presented with severe CS and hyperestronemia, manifesting clinically with a Cushingoid appearance, gynecomastia, and telangiectasias. Analysis of adrenal tissues following bilateral adrenalectomy showed high expression of P450 aromatase (CYP19A1). The patient carried a germline non-sense pathogenic variant in ARMC5 (p.R173*), with two independent somatic pathogenic variants identified in the right (p.S571*) and left (p.Q235*) adrenal tissues, respectively. The expression of ARMC5 was drastically decreased in the hyperplastic regions when compared to either the adjacent non-hyperplastic regions and samples from PBMAH without pathogenic variants in ARMC5. We found expression of CYP19A1 in other cases of PBMAH, although there were no differences in aromatase expression between ARMC5-mutant and ARMC5-non-mutant cases. We conclude that in select cases, PBMAH can be associated with aromatase expression resulting in elevated estrogens, irrespective of sex. Additionally, CYP19A1 expression does not appear to depend on the ARMC5 variant status.

Activation of the Kinin B1 Receptor by Its Agonist Reduces Melanoma Metastasis by Playing a Dual Effect on Tumor Cells and Host Immune Response.

Metastatic melanoma is an aggressive type of skin cancer leading half of the patients to death within 8-10 months after diagnosis. Kinins are peptides that interact with B1 and B2 receptors playing diverse biological roles. We investigated whether treatment with B1 receptor agonist, des-Arg9-bradykinin (DABK), has effects in lung metastasis establishment after melanoma induction in mice. We found a lower number of metastatic colonies in lungs of DABK-treated mice, reduced expression of vascular cell adhesion molecule 1 (VCAM-1), and increased CD8+T-cell recruitment to the metastatic area compared to animals that did not receive treatment. To understand whether the effects of DABK observed were due to the activation of the B1 receptor in the tumor cells or in the host, we treated wild-type (WT) and kinin B1 receptor knockout (B1-/-) mice with DABK. No significant differences in the number of melanoma colonies established in lungs were seen between WT and B1-/-mice; however, B1-/-mice presented higher VCAM-1 expression and lower CD8+T-cell infiltration. In conclusion, we believe that activation of kinin B1 receptor by its agonist in the host stimulates the immune response more efficiently, promoting CD8+T-cell recruitment to the metastatic lungs and interfering in VCAM-1 expression. Moreover, treatment with DABK reduced establishment of metastatic colonies by mainly acting on tumor cells; hence, this study brings insights to explore novel approaches to treat metastatic melanoma targeting the B1 receptor.

Effect of iron on the dissolution of bovine enamel powder in vitro by carbonated beverages.

OBJECTIVES: The aim of this study was to evaluate, in vitro, the effect of iron on the dissolution of bovine enamel powder, when added to two carbonated beverages. DESIGN: Powdered enamel was produced by griding enamel fragments of bovine incisor in a steel pestle and mortar. Particles between 75 and 106 microm were selected using appropriated meshes. At time zero, the carbonated beverage (Coke or Sprite Zero) was added to powdered enamel (1 mg enamel powder/10 microL of beverage) and vortexed for 30 s. The sample was immediately centrifuged (11,000 rpm) for 30 s and the supernatant was removed at 1 min 40 s. This procedure was repeated five times with the beverage containing increasing ferrous sulphate concentrations (1.25, 2.5, 5, 10, 15, 30 and 60 mmol/L). The phosphate released in the medium was analysed spectrophotometrically. Data were analysed using ANOVA and Tukey's test (p<0.05). RESULTS: When iron at 30 and 60 mmol/L was added to Coke, a significant reduction in the dissolution of powdered enamel was observed when compared to control (11 and 17%, respectively), while lower iron concentrations did not have any effect on enamel powder dissolution. Regarding Sprite Zero, iron concentrations up to 10 mmol/L had no significant effect, while higher concentrations significantly increased enamel powder dissolution. CONCLUSIONS: The results suggest that iron can interfere with the dissolution of dental enamel powder in the presence of acidic beverages and the type of acid in these beverages seems to modulate this effect.

Absence of DNA damage in multiple organs (blood, liver, kidney, thyroid gland and urinary bladder) after acute fluoride exposure in rats.

Fluoride has been widely used in dentistry as a caries prophylactic agent. However, there has been some speculation that excess fluoride could cause an impact on genome integrity. In the current study, the potential DNA damage associated with exposure to fluoride was assessed in cells of blood, liver, kidney, thyroid gland and urinary bladder by the single cell gel (comet) assay. Male Wistar rats aging 75 days were distributed into seven groups: Groups 1 (control), 2, 3, 4, 5, 6 and 7 received 0 (deionized water), 10, 20, 40, 60, 80 and 100 mgF/Kg body weight from sodium fluoride (NaF), respectively, by gastrogavage. These groups were killed at 2 h after the administration of the fluoride doses. The level of DNA strand breaks did not increase in all organs evaluated and at all doses of NaF tested, as depicted by the mean tail moment. Taken together, our results suggest that oral exposure to NaF did not result in systemic genotoxic effect in multiple organs related to fluoride toxicity. Since DNA damage is an important step in events leading to carcinogenesis, this study represents a relevant contribution to the correct evaluation of the potential health risk associated with chemical exposure.

Effect of iron supplementation on the erosive potential of carbonated or decarbonated beverage.

This study evaluated, in vitro, the effect of iron (previously exposed with enamel powder or added directly to the beverage) on the erosive potential of carbonated or decarbonated beverage. Four sets of experiments were done. For groups E1 and E3, a solution containing 30 mmol/L FeSO4 was added to bovine enamel powder (particles between 75-106 mm) before exposure to the carbonated or decarbonated beverage (Sprite Zero(R)), respectively. For groups E2 and E4, 15 mmol/L FeSO4 was added directly to the carbonated or decarbonated beverage, respectively. Control groups were included for comparison. In controls C1 and C3, the experiments E1 and E3 were repeated, but the iron solution was replaced by deionized water. For controls C2 and C4, the carbonated and decarbonated beverage, respectively, was used, without addition of iron. After addition of the beverage to the powdered enamel (40 mg enamel powder/400 mL of final volume), the sample was vortexed for 30 s and immediately centrifuged for 30 s (11,000 rpm). The supernatant was removed after 1 min 40 s. This procedure was repeated in quintuplicate and the phosphate released was analyzed spectrophotometrically. The results were analyzed by Student's t-test (p<0.05). E2 presented the best results with a significant inhibition (around 36%) of phosphate released. For E3 and E4 a non-significant inhibition (around 4 and 12%, respectively), was observed. For E1 an increase in phosphate loss was detected. Thus, the protective effect of iron seems to be better when this ion is directly added to the carbonated beverage.

Fluoridation of the public water supply and prevalence of dental fluorosis in a peripheral district of the municipality of Bauru, SP.

OBJECTIVES: The objectives of this study were to assess the fluoride concentration in the public water supply and the prevalence of dental fluorosis in schoolchildren between 7 and 15 years old, living in a peripheral district of the municipality of Bauru. MATERIAL AND METHODS: For this, fifty two water samples were collected on three different days of one week. These samples were analyzed for fluoride by means of the ion-sensitive electrode method (Orion 9609) coupled to a potentiometer (Procyon, model 720). In this method, 1.0 mL of TISAB II (Orion) was added to 1.0 mL of the sample. For the epidemiological survey of fluorosis, 52 schoolchildren of both genders, aged between 7 and 15 were assessed, with prior authorization from their caretakers. Only one person examined the children, after supervised toothbrushing and drying with cotton wool rolls. The TF index was used. RESULTS: The fluoride concentrations in the water samples ranged from 0.62 to 1.20 mg/L, with a mean of 0.9 mg/L. The prevalence of dental fluorosis was 33%, with severity ranging from TF1 to TF4 (Kappa of 0.73 and concordance of 83.33%). CONCLUSIONS: The results from the analysis of water samples indicated a fluoride concentration greater than recommended for Bauru. The fluorosis levels found were higher than expected for a peripheral district, in which water is one of the few sources of fluoride.

Effect of iron supplementation on the erosive potential of carbonated or decarbonated beverage

This study evaluated, in vitro, the effect of iron (previously exposed with enamel powder or added directly to the beverage) on the erosive potential of carbonated or decarbonated beverage. Four sets of experiments were done. For groups E1 and E3, a solution containing 30 mmol/L FeSO4 was added to bovine enamel powder (particles between 75-106 mm) before exposure to the carbonated or decarbonated beverage (Sprite Zero®), respectively. For groups E2 and E4, 15 mmol/L FeSO4 was added directly to the carbonated or decarbonated beverage, respectively. Control groups were included for comparison. In controls C1 and C3, the experiments E1 and E3 were repeated, but the iron solution was replaced by deionized water. For controls C2 and C4, the carbonated and decarbonated beverage, respectively, was used, without addition of iron. After addition of the beverage to the powdered enamel (40 mg enamel powder/400 mL of final volume), the sample was vortexed for 30 s and immediately centrifuged for 30 s (11,000 rpm). The supernatant was removed after 1 min 40 s. This procedure was repeated in quintuplicate and the phosphate released was analyzed spectrophotometrically. The results were analyzed by Student's t-test (p<0.05). E2 presented the best results with a significant inhibition (around 36 percent) of phosphate released. For E3 and E4 a non-significant inhibition (around 4 and 12 percent, respectively), was observed. For E1 an increase in phosphate loss was detected. Thus, the protective effect of iron seems to be better when this ion is directly added to the carbonated beverage.

Conhecimento dos médicos pediatras e odontopediatras de Bauru e Marília a respeito de flúor / Knowledge of pediatric doctors and dentists from Bauru and Marília about fluoride

A proposta deste trabalho foi verificar o conhecimento dos médicos pediatras e odontopediatras, a respeito dos compostos fluoretados. Para tanto, foram visitados 91 médicos pediatras e 72 odontopediatras dos municípios de Bauru e Marília, que ao concordarem em participar da pesquisa receberam um questionário com 22 questões. O preenchimento e a devolução foram imediatos. Os dados obtidos foram analisados por meio de estatística descritiva, utilizando freqüências absolutas e relativas, representadas através de tabelas. Mediante a análise dos questionários, verificou-se que alguns polivitamínicos que contêm flúor são usualmente prescritos pelos médicos pediatras, ao passo que os géis, vernizes e soluções para bochecho são bastante empregados pelos odontopediatras. Não foi estabelecida relação entre o conhecimento e tempo de formado, a idade do profissional, a universidade de origem, a cidade em que trabalha e a área de atuação (particular, rede pública ou em ambos) desses profissionais. Os resultados obtidos sugerem que o conhecimento dos médicos pediatras e odontopediatras, das cidades de Bauru e de Marília, a respeito da presença de flúor em várias fontes de ingestão se mostrou insuficiente e, em algumas situações, preocupante, com relação à prevenção de fluorose dentária.

Fluoridation of the public water supply and prevalence of dental fluorosis in a peripheral district of the municipality of Bauru, SP

OBJECTIVES: The objectives of this study were to assess the fluoride concentration in the public water supply and the prevalence of dental fluorosis in schoolchildren between 7 and 15 years old, living in a peripheral district of the municipality of Bauru. MATERIAL AND METHODS: For this, fifty two water samples were collected on three different days of one week. These samples were analyzed for fluoride by means of the ion-sensitive electrode method (Orion 9609) coupled to a potentiometer (Procyon, model 720). In this method, 1.0 mL of TISAB II (Orion) was added to 1.0 mL of the sample. For the epidemiological survey of fluorosis, 52 schoolchildren of both genders, aged between 7 and 15 were assessed, with prior authorization from their caretakers. Only one person examined the children, after supervised toothbrushing and drying with cotton wool rolls. The TF index was used. RESULTS: The fluoride concentrations in the water samples ranged from 0.62 to 1.20 mg/L, with a mean of 0.9 mg/L. The prevalence of dental fluorosis was 33 percent, with severity ranging from TF1 to TF4 (Kappa of 0.73 and concordance of 83.33 percent). CONCLUSIONS: The results from the analysis of water samples indicated a fluoride concentration greater than recommended for Bauru. The fluorosis levels found were higher than expected for a peripheral district, in which water is one of the few sources of fluoride.

OBJETIVOS: Avaliar a concentração de flúor na água de abastecimento público e a prevalência de fluorose dentária de escolares entre 7 e 15 anos de idade, residentes em um bairro da periferia de Bauru. MATÉRIAL E MÉTODOS: Foram coletadas 52 amostras de água durante três dias de uma semana e analisadas utilizando-se o eletrodo íon sensível (Orion 9609), acoplado a um potenciômetro (Procyon, modelo 720), com 1,0 mL da amostra à qual foi adicionado 1,0 mL de TISAB II (Orion). Para o levantamento epidemiológico de fluorose foram examinados 52 escolares entre 7 e 15 anos de idade, de ambos os gêneros, mediante a obtenção de autorização prévia dos responsáveis. Somente um examinador realizou os exames após escovação supervisionada e secagem dos dentes com rolos de algodão. O índice utilizado foi o TF, estabelecido a partir do grau máximo verificado em cada indivíduo. RESULTADOS: A concentração de flúor na água variou entre 0,62 e 1,15 mg/L, mantendo uma média de 0,9 mg/L. A prevalência de fluorose dentária verificada foi de 33 por cento, com severidade variando entre TF1 e TF4 (Kappa=0,73 e concordância de 83,33 por cento). CONCLUSÕES: Os resultados da análise das amostras de água indicam uma concentração média de flúor acima do recomendado para Bauru. O índice de fluorose dentária verificado foi maior que o esperado para um bairro da periferia, onde a água é uma das poucas fontes de ingestão de flúor.

Fluoridation of the public water supply and prevalence of dental fluorosis in a peripheral district of the municipality of Bauru, SP%Fluoretação da água de abastecimento público e prevalência de fluorose dentária em bairro da periferia de Bauru, SP

OBJETIVOS: Avaliar a concentração de flúor na água de abastecimento público e a prevalência de fluorose dentária de escolares entre 7 e 15 anos de idade, residentes em um bairro da periferia de Bauru. MATÉRIAL E MÉTODOS: Foram coletadas 52 amostras de água durante três dias de uma semana e analisadas utilizando-se o eletrodo íon sensível (Orion 9609), acoplado a um potenciômetro (Procyon, modelo 720), com 1,0 mL da amostra à qual foi adicionado 1,0 mL de TISAB II (Orion). Para o levantamento epidemiológico de fluorose foram examinados 52 escolares entre 7 e 15 anos de idade, de ambos os gêneros, mediante a obtenção de autorização prévia dos responsáveis. Somente um examinador realizou os exames após escovação supervisionada e secagem dos dentes com rolos de algodão. O índice utilizado foi o TF, estabelecido a partir do grau máximo verificado em cada indivíduo. RESULTADOS: A concentração de flúor na água variou entre 0,62 e 1,15 mg/L, mantendo uma média de 0,9 mg/L. A prevalência de fluorose dentária verificada foi de 33 por cento, com severidade variando entre TF1 e TF4 (Kappa=0,73 e concordância de 83,33 por cento). CONCLUSÕES: Os resultados da análise das amostras de água indicam uma concentração média de flúor acima do recomendado para Bauru. O índice de fluorose dentária verificado foi maior que o esperado para um bairro da periferia, onde a água é uma das poucas fontes de ingestão de flúor